Ethanol is metabolized in the liver by alcohol dehydrogenase to acetaldehyde, and acetaldehyde is then further metabolized by aldehyde dehydrogenase to acetate. Most emphasis in the study of the metabolites of ethanol has focused on acetaldehyde. However, the blood concentration of this compound rarely exceeds 10 MuM, while the blood concentration of acetate approaches 2 mM even after the consumption of moderate amounts of ethanol. This study was undertaken to elucidate the consequences of acetate metabolism on the major metabolic pathways. Administration of acetate to starved rats causes a number of changes in hepatic metabolite concentrations, the most striking of which are (1) a greater than one hundredfold elevation in pyrophosphate concentration, (2) a fivefold elevation in calcium, (3) a marked reduction in the cytosolic [NADP-+]/[NADPH] redox ratio, and (4) a twofold increase in glucose concentration.